(a) Field of the Invention
This invention relates to a programmable tracking pressure regulator and method particularly useful for pressure control in apparatus utilizing the formation, control and movement of small volumes of liquid. More particularly, this invention relates to a programmable tracking pressure regulator and method capable of high-precision pressure control in microfluidic networks, even at high operating pressures, for uses such as capillary chromatography.
(b) Description of Prior Art
Fluid transport in microfluidic circuits is normally effected in one of two ways: either by applying pressure differences between selected points in the circuit, or by applying voltage differences between selected points. The application of pressure results in the classical Hagen-Poiseuille laminar flow distribution in capillaries, whereas the application of voltage results in electrokinetic pumping and plug flow. In both cases, however, the control of fluid transport at the scale of capillaries has been handicapped by the absence of microscopic fluid gates. In branched fluid circuits, in the absence of a means to stop the flow in certain directions, there is no way to isolate different parts of the fluid circuit.
It has been proposed to provide mechanical gates in capillary circuits, wherein the valve closures consist of diaphragms or similar sealing members. However, at capillary scales the mechanical valves are unreliable and difficult to fabricate, particularly if alignment is required between parts. Mechanical valves have not been useful at the scale of nanoliter volumes.
It has also been proposed to use non-mechanical means to control fluid movements in capillaries. For example, the concept of utilizing menisci to control fluid movements in capillaries has been utilized in devices such as in the Lang-Levy micropipette.
U.S. Pat. No. 6,193,471, the disclosure of which is hereby incorporated by reference, discloses a controllable method for creating menisci in a liquid capillary, for removing menisci from a liquid capillary, and for external control of the hydrostatic pressure within a capillary segment. More specifically, the ""471 patent discloses a process and system for transporting small volumes of liquid samples such as at the nanoliter level. The process and system permits the inclusion and/or the removal of menisci from a liquid sample and also permits the transport of exact small volumes of liquid sample from a storage means to a point of use in order to permit precise treatment of the sample such as for analysis or reaction.
Pressure balancing can be used to control fluid transport in capillary networks as described in the ""471 patent. A shallow, disk-shaped cavity or xe2x80x9cdonutxe2x80x9d positioned along the track of a capillary will cause a liquid stream to split and flow around the periphery of the cavity. A separate channel perpendicular to the disk along the axis of the disk allows pressure access to the liquid. An external pressure source can be impressed on the meniscus of the split-stream of the liquid, thereby controlling the hydrostatic pressure of the liquid in the capillary. When control cavities or xe2x80x9cdonutsxe2x80x9d are placed at opposite ends of a capillary, they can be employed to produce a pressure gradient along that capillary that directs movement of liquid through the capillary. More specifically, a storage volume having a height of a capillary is in fluid communication with at least two capillary conduits. The storage volume has a width larger than the width of a capillary so that the storage volume is capable of retaining a larger volume of liquid as compared to the volume stored in a capillary. The storage volume also is in fluid communication with a gas having a controlled pressure thereby permitting the storage volume to function as a pressure control point on a liquid in the storage volume. A meniscus is formed within the storage volume at the interface of a liquid directed to the storage volume from an inlet capillary conduit and the gas supplied to the storage volume. The liquid is passed from the storage volume into an outlet capillary conduit. The liquid in the outlet capillary conduit extends from the storage volume to a capillary gate at the end of the outlet capillary conduit, where a second meniscus is formed on the liquid surface in the outlet capillary conduit. The capillary gate functions as a valve. Control of liquid flow is based on the fact that the meniscus forces at the capillary gate arrest the flow of liquid in the outlet capillary conduit unless hydrostatic pressure exerted on the liquid in the outlet capillary conduit exceeds the meniscus forces.
For certain applications, such as providing the pressure differentials between microfluidic donuts, the control pressure differentials must be fairly small. At feature dimensions on the order of micrometers, the meniscus pressure in a capillary is about 1 psi. In order to use donuts and capillary forces at higher pressures, especially at the much higher pressures typical of high performance liquid chromatography, there must be some means for programmable, high-precision pressure control (e.g., xc2x10.01 to xc2x10.1 psi resolution on a common mode pressure of 2000 psi). The response time must be fast (e.g., within tenths of a second), but programmable control implies that the regulator must be able to rapidly increase or decrease the pressure as the circumstances dictate. In some cases, the regulator must be able to pull the pressure below atmospheric pressure.
It therefore would be desirable to provide a programmable, high-precision pressure regulator suitable for controlling small pressure differentials in microfluidic circuits notwithstanding the presence of relatively high common mode pressures.
The problems of the prior art have been overcome by the present invention, which provides a regulator for high precision control of pressure based on a means of measuring pressure differentials. More specifically, the present invention provides a pressure control that tracks a relatively high background pressure and applies a positive or negative offset to create the small pressure differentials that can be utilized to transport fluids within a capillary network. The present invention is also directed to a method of controlling pressure differences between connected pressure control nodes (such as donut cavities) with a high degree of precision. This is accomplished using tracking pressure regulators to measure and respond to the difference between a liquid pump pressure and a regulated pneumatic pressure.
Features
The present invention provides a compact, rugged, low cost, regulator for high precision control of pressure.
The present invention also provides a means of measuring multiple pressure differentials.
The present invention also provides a means of measuring multiple pressure differentials under a high common mode pressure.
The present invention also provides a means of controlling multiple pressure differentials.
The present invention also provides a means of controlling multiple pressure differentials under a high common mode pressure.
The present invention also provides an individually programmable means of controlling multiple pressure differentials under a high common mode pressure.
The present invention also provides a temperature compensated means of controlling multiple pressure differentials under a high common mode pressure.
The present invention also provides a means of controlling multiple pressures that track a relatively high background pressure, and applying positive or negative offsets to create small pressure differentials.
The present invention also provides a method of sensing and measuring very small pressure differences between very small volumes.
The present invention also provides a means of easily and rapidly changing the composition of the control fluid without danger of contamination.